Monoclonal antibodies: the story of a discovery that revolutionized science and medicine

Angiostatin-Like Activity of a Monoclonal Antibody to the Catalytic Subunit of F1F0 ATP Synthase

“…Inhibition of cell surface ATP synthase by angiostatin reduces cellular proliferation, and in combination with low extracellular pH (pH e ), intracellular acidification and cytotoxicity ensue (6)(7)(8)(16)(17)(18). Similar results were achieved with polyclonal antibodies targeting ATP synthase (6)(7)(8)12).…”

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

“…Many of the disease-specific or pathogenic molecules are revealed as detectable and even 'druggable targets' by highly selective proteins, such as mAbs (1,2).…”

Trial Watch: Monoclonal antibodies in cancer therapy

“…16 Irrespective of these considerations, antibodies of all types (murine, chimeric and human) have been approved by FDA and by other international regulatory agencies for the treatment of several pathologies, including (but not limited to) autoimmune diseases and cancer. 2,4 Just to mention a few examples: muromonab-the first mAb ever approved for use in humans (for the therapy of transplant rejection)-is murine, 17 infliximab-an anti-TNFα mAb that is currently employed against rheumatoid arthritis and Crohn's disease-is chimeric, 18,19 and ofatumumab-an anti-CD20 mAb that is used for the therapy of chronic lymphocytic leukemia-is entirely human. 20 Interestingly, the suffix of the international non-proprietary names for mAbs denotes the antibody format, as follows: -omab, mouse IgG2; -ximab, chimeric IgG1; -zumab, humanized IgG1; -umab, human antibody from phage display or transgenic mice technology; -axomab, trifunctional (bispecific) mouse-rat hybrid mAb; -cept, Fc fusion protein; -stim, Fc fusion peptide ( Table 1).…”

“…Moreover, mAbs have already been successfully employed in vivo (in animal models of disease or patients) to: (i) neutralize circulating factors, (ii) activate immune effector mechanisms against Most mAbs that are currently approved for use in humans (irrespective of their indication) or under clinical evaluation belong to the IgG isotype. 2,4 There are at least six classes of mAbs that are relevant for cancer therapy: (i) mAbs that directly inhibit tumor cellautonomous pro-survival cascades (e.g., cetuximab and panitumumab, which inhibit the epidermal growth factor receptor, EGFR, and are currently approved for the treatment of colorectal cancer); 21 (ii) mAbs that interfere with the tumor-stroma interaction, thereby indirectly inhibiting tumor growth (e.g., bevacizumab, which blocks the vascular endothelial growth factor, VEGF, and is currently employed in the for the therapy of colorectal, breast, renal and lung cancer); [22][23][24] (iii) mAbs that bind to antigens expressed on the surface of tumor cells and function by selectively engaging immune effector mechanisms such as ADCC, 4,5 ADCP, 25 and CDC 6,7 (e.g., rituximab, a naked anti-CD20 in use for the therapy of lymphoma); 26,27 (iv) trifunctional (bispecific) mAbs, which can bind two different antigens while remaining capable of engaging immune effector functions (e.g., catumaxomab, an anti-CD3, anti-EpCAM chimeric mAb currently approved for the treatment of malignant ascites in patient with EpCAM + neoplasms); 28 (v) immunoconjugates (e.g., 90 Y-ibritumomab tiuxetan and 131 I-tositumomab, radionuclide-coupled anti-CD20 mAbs that are used for the therapy of lymphoma); 29,30 and (vi) immunostimulatory mAbs, i.e., mAbs that facilitate the development of a tumor-specific immune response by targeting the cancer cell/immune system crosstalk and the signaling pathways that this crosstalk elicits. An interesting sub-group encompassing these latter two categories is represented by immunoconjugates between putative tumor antigens and mAbs that target receptors expressed on the surface of dendritic cells (DCs), including CLEC9A, DC-SIGN, DEC205.…”

“…Compared with their polyclonal counterparts, which are obtained from the serum of animals upon immunization, mAbs are advantageous in that they exhibit a much higher specificity and are less prone to contamination by pathogens. 2 Thus, the monoclonal antibody technology has generated or considerably improved uncountable diagnostic applications, including (but not limited to) epitope-specific immunoblotting, immunofluorescence and immunohistochemistry. Moreover, mAbs have already been successfully employed in vivo (in animal models of disease or patients) to: (i) neutralize circulating factors, (ii) activate immune effector mechanisms against Most mAbs that are currently approved for use in humans (irrespective of their indication) or under clinical evaluation belong to the IgG isotype.…”